Bordetella Adenylate Cyclase Toxin Inhibits Monocyte-to-Macrophage Transition and Dedifferentiates Human Alveolar Macrophages into Monocyte-like Cells

Author:

Ahmad Jawid Nazir1,Holubova Jana1,Benada Oldrich2,Kofronova Olga2,Stehlik Ludek3,Vasakova Martina3,Sebo Peter1

Affiliation:

1. Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the CAS, Prague, Czech Republic

2. Laboratory of Molecular Structure Characterization, Institute of Microbiology of the CAS, Prague, Czech Republic

3. Department of Respiratory Medicine, Thomayer Hospital, Prague, Czech Republic

Abstract

Macrophages are key sentinel cells of the immune system, and, as such, they are targeted by the toxins produced by the pertussis agent Bordetella pertussis . The adenylate cyclase toxin (CyaA) mediates immune evasion of B. pertussis by suspending the bactericidal activities of myeloid phagocytes. We reveal a novel mechanism of potential subversion of host immunity, where CyaA at very low (22 pM) concentrations could inhibit maturation of human monocyte precursors into the more phagocytic macrophage cells. Furthermore, exposure to low CyaA amounts has been shown to trigger dedifferentiation of mature primary human alveolar macrophages back into monocyte-like cells. This unprecedented capacity is likely to promote survival of the pathogen in the airways, both by preventing maturation of monocytes attracted to the site of infection into phagocytic macrophages and by dedifferentiation of the already airway-resident sentinel cells.

Funder

Czech Science Foundation

Agency for Health Research of the Czech Republic

Ministry of Education, Youth and Sports of the Czech Republic

Ministry of Education, Youth and Sports of the Czech Republic - EATRIS-CZ

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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